Low methylation rates of dopamine receptor D2 gene promoter sites in Japanese schizophrenia subjects

Abstract

Objectives: According to the dopamine hypothesis, several studies on the gene for the dopamine receptor D2 (DRD2) have been conducted. However, no trait biomarkers on DRD2 are available. We examined whether the methylation rates in the upstream region of DRD2 in leukocytes are different in schizophrenia (SCZ) subjects compared to control subjects.

Methods: We selected seven CpG sites in the upstream region of DRD2 that may theoretically bind major transcription factors. The methylation rates in these regions of 50 medicated and 18 drug-naïve SCZ subjects were compared with those of age-matched control subjects.

Results: The methylation rates were significantly lower in medicated (CpG2, P < 0.0001; CpG4, P = 0.013; CpG7, P < 0.0001; and average: 12.9 ± 1.8 vs. 14.1 ± 2.2, P = 0.005) and drug-naïve SCZ subjects (CpG1, P = 0.006; CpG2, P = 0.001; CpG3, P = 0.001; CpG5, P = 0.02; CpG6, P = 0.015; CpG7, P = 0.027; and average: 9.86 ± 0.9 vs. 11.2 ± 1.3, P = 0.002).

Conclusions: We confirmed low methylation rates in the upstream region of DRD2 in both medicated and drug-naïve SCZ subjects. Low methylation rates of DRD2 in leukocytes may be a trait biomarker for SCZ.

Keywords:

• Biomarker
• dopamine receptor D2 gene
• pyrosequencer
• methylation
• schizophrenia

Acknowledgments

We wish to thank Ms. Chiemi Onishi for technical assistance.

Statement of interest

None to declare.

Funding information

This work was partially supported by a Health and Labour Science Research Grant from the Japanese Ministry of Health, Labour and Welfare and a Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology, JSPS KAKENHI Grant Number 15K09808.